Phenobarbital (INN) or phenobarbitone (former BAN) is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the benzodiazepines for these indications. The World Health Organization recommends its use as first-line for partial and generalized tonic-clonic seizures (those formerly known as Grand Mal) in developing countries. It is a core medicine in the WHO Model List of Essential Medicines, which is a list of minimum medical needs for a basic health care system. In more affluent countries it is no longer recommended as a first-line medication, however it is relied on as an alternate when a patient fails to respond to treatment with more modern AED's (Anti-Epileptic-Drugs). It is still commonly used around the world to treat neonatal seizures.
Phenobarbital's soporific, sedative and hypnotic properties were well known in 1912, but nobody knew it was also an effective anticonvulsant. The young doctor Alfred Hauptmann gave it to his epilepsy patients as a tranquiliser and discovered that their epileptic attacks were susceptible to the drug. Hauptmann performed a careful study of his patients over an extended period. Most of these patients were using the only effective drug then available, bromide, which had terrible side effects and limited efficacy. On phenobarbital, their epilepsy was much improved: The worst patients suffered fewer and lighter seizures and some patients became seizure free. In addition, they improved physically and mentally as bromides were removed from their regime. Patients who had been institutionalised due to the severity of their epilepsy were able to leave and, in some cases, resume employment. Hauptman dismissed concerns that its effectiveness in stalling epileptic attacks could lead to patients suffering a build-up that needed to be "discharged". As he expected, withdrawal of the drug lead to an increase in seizure frequency – it was not a cure. The drug was quickly adopted as the first widely effective anticonvulsant, though World War I delayed its introduction in the U.S.
Between 1934-1945 Phenobarbital, under the brand name Luminal, was used by German doctors under the Nazi party endorsed policy of eugenics to kill children born with disease or deformities. Code-named Operation T-4, this policy of murdering German-born children and adults deemed not to meet the standards of the Aryan race was a pre-cursor to the Holocaust and many of the medical staff involved were later to transfer to Nazi Concentration Camps where their expertise in killing was put to further use.
In 1940, Winthrop Chemical produced sulfathiazole tablets that were contaminated with phenobarbital. This occurred because both tablets were produced side-by-side and equipment could be interchanged. Each antibacterial tablet contained more than twice the required dose of phenobarbital necessary to induce sleep. Hundreds of patients died or were injured as a result. A U.S. Food and Drug Administration investigation was highly critical of Winthrop and the scandal lead to the introduction of Good Manufacturing Practice for drugs.
The drug predates the FDA approval processes and has failed to be formally cleared for use in subsequent years. Guidance was issued in June 2006 of plans to enforce US approval for unapproved drugs.
Phenobarbital was used for over 25 years as prophylaxis in the treatment of febrile seizures. Although an effective treatment in preventing recurrent febrile seizures, it had no positive effect on patient outcome or risk of developing epilepsy. The treatment of simple febrile seizures with anticonvulsant prophylaxis is no longer recommended.
The first line drugs for treatment of status epilepticus are fast acting benzodiazepines such as diazepam or lorazepam. If these fail then phenytoin may be used, with phenobarbital being an alternative in the U.S. but used only third line in the UK. Failing that, the only treatment is anaesthesia in intensive care.
Phenobarbital is the first line choice for the treatment of neonatal seizures. Concerns that neonatal seizures in themselves could be harmful make most physicians treat them aggressively. There is, however, no reliable evidence to support this approach.
Phenobarbital causes a "depression" of the body's systems, mainly the central and peripheral nervous systems; thus, the main characteristic of phenobarbital overdose is a "slowing" of bodily functions, including decreased consciousness (even coma), bradycardia, bradypnea, hypothermia, and hypotension (in massive overdoses). Overdose may also lead to pulmonary edema and acute renal failure as a result of shock.
The electroencephalogram of a person with phenobarbital overdose may show a marked decrease in electrical activity, to the point of mimicking brain death. This is due to profound depression of the central nervous system, and is usually reversible.
Treatment of phenobarbital overdose is supportive, and consists mainly in the maintenance of airway patency (through endotracheal intubation and mechanical ventilation), correction of bradycardia and hypotension (with intravenous fluids and vasopressors, if necessary) and removal of as much drug as possible from the body. Depending on how much time has elapsed since ingestion of the drug, this may be accomplished through gastric lavage (stomach pumping) or use of activated charcoal. Hemodialysis is effective in removing phenobarbital from the body, and may reduce its half-life by up to 90%. There is no specific antidote for barbiturate poisoning.
British veterinarian Donald Sinclair, better known as "Sigfried Farnon" in the "All Creatures Great and Small" books of James Herriot committed suicide at the age of 84 by injecting himself with an overdose of phenobarbital. Activist Abbie Hoffman also committed suicide by consuming phenobarbital, combined with alcohol, on April 12, 1989; the residue of around 150 pills was found in his body at autopsy.